Effects of lamotrigine on mood in older adults with epilepsy and co-morbid depressive symptoms: an open-label, multicentre, prospective study.
ABSTRACT Both epilepsy and depressive symptoms are more prevalent in older individuals than in any other age group. Furthermore, depressive symptoms are among the most common interictal psychiatric co-morbid disorders in people with epilepsy. For these reasons, pharmacological treatment of epilepsy that might also confer antidepressant effects may be particularly beneficial in older patients. In this respect, lamotrigine is of considerable interest amongst antiepileptic drugs (AEDs) because it has proven thymoleptic activity.
These analyses, conducted on a data set drawn from a previously reported, open-label, multicentre, prospective study, examined the effect of lamotrigine on mood in adults aged>or=50 years with epilepsy and co-morbid depressive symptoms. All subjects were receiving background AED therapy at baseline.
Of the 158 subjects enrolled in the initial study, 40 adults (24 women, 16 men) met the age criterion for these analyses. The study consisted of a screening/baseline phase and four treatment phases over 36 weeks: lamotrigine escalation phase (7 weeks); lamotrigine maintenance or adjunctive therapy phase (12 weeks); concomitant AED withdrawal phase (5 weeks); and lamotrigine monotherapy phase (12 weeks). Psychometric evaluation of mood utilized the Beck Depression Inventory (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E) and the Profile of Mood States (POMS). Scores at the end of the adjunctive and monotherapy phases were compared with baseline scores. Lower scores on these scales indicate less depressive symptomatology.
Mean baseline scores for the BDI-II, CES-D, NDDI-E and POMS were 15.8, 24.3, 13.8 and 57.7, respectively. Change scores were statistically significant (p<0.01) compared with baseline at the end of the adjunctive and monotherapy phases for all four psychometric measures of mood, with the exceptions of BDI-II and NDDI-E at the end of the adjunctive phase.
The older adults in these analyses presented with low to moderate levels of depressive symptoms. Addition of lamotrigine to background AED therapy demonstrated antidepressant activity similar to that for the whole sample in the initial study. Given that the onset and prevalence of epilepsy are higher in older adults than in any other age group, pharmacological treatment for epilepsy in older patients that might also confer antidepressant therapy may be particularly beneficial.
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ABSTRACT: The World Health Organization (WHO) report has predicted that major depression will become a key cause of illness-induced disability by the year 2020, second only to ischemic heart diseases. Although a large number of antidepressant drugs (from monoamine oxidase inhibitors and tricyclic antidepressants to dual reuptake inhibitors) are available for treatment of the disease, approximately 30% of patients failed to respond to this therapy. Therefore, the search for newer or novel drug targets for the treatment of major depression continues. Some of these targets include dopamine, triple reuptake inhibition, L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, sigma-1 receptors, neurosteroids, melatonin, glutamate, 5HT6, 5HT7 serotonin receptor antagonists, beta-3 adrenoceptor antagonist, vasopressin V(Ib) receptor antagonists, NK2 tachykinin receptor antagonists, glucocorticoid receptor antagonists and corticotropin-releasing factor-1 receptor antagonists, as well as herbal antidepressant drugs. The present review attempts to discuss the status of some of these novel approaches and the drugs that are under investigation for the treatment of major depression. An attempt is also made to review the status of three indigenous plant-derived drugs, berberine, curcumin and rutin, as novel and safe future herbal antidepressants. There is an exciting future in the discovery of novel targets and target-specific agents for the management of major depression.Expert Opinion on Investigational Drugs 06/2009; 18(6):767-88. DOI:10.1517/13543780902880850 · 5.43 Impact Factor
- The Journal of neuropsychiatry and clinical neurosciences 02/2011; 23(1):E32. DOI:10.1176/appi.neuropsych.23.1.E32 · 2.77 Impact Factor
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ABSTRACT: INTRODUCTION: Psychiatric comorbidities (such as depression, anxiety, psychosis, inattention, obsession, personality traits, aggression and suicide) are frequent in patients with epilepsy and have a significant impact on medical management and quality of life. AREAS COVERED: A literature search was performed in MEDLINE for epidemiological, longitudinal, prospective, double-blind clinical trial studies published between 1990 and 2011 using the following words: epilepsy, antiepileptic drugs (AEDs), behavioral/emotional/psychiatric comorbidities, suicide and aggression. In this review, the author discusses: i) the characterization and prevalence of behavioral disturbances associated with epilepsy, ii) variables correlated with behavioral comorbidities which include: psychosocial-, clinical- and treatment-related variables, iii) the complex mechanisms of behavioral comorbidities associated with epilepsy, which include both psychosocial (functional) and organic; the process of epileptogenesis, neuronal plasticity, abnormalities in hypothalamic-pituitary axis and neurotransmitters and pathways are fundamental determinants, iv) the negative psychotropic effects of AEDs and their mechanisms and v) the suggested biopsychosocial model of management (pharmacological and non-pharmacological). EXPERT OPINION: The relationship between psychiatric disorders and epilepsy has relevant therapeutic implications which should be directed towards a comprehensive biopsychosocial approach that focuses on the whole person rather than simply on the disease process.Expert Opinion on Drug Safety 05/2011; 10(6):913-34. DOI:10.1517/14740338.2011.588597 · 2.74 Impact Factor